"Neurovascular coupling" appears to be a critical mechanism
in the regulation of ocular blood flow (OBF).
Increased activity of the neurons subserving vision leads to higher blood flows to the neural elements, a response called “functional hyperemia”. This intertwined association of the nerves and blood flow is called “neurovascular coupling”. This phenomenon is defined as the "vascular response to increased neuronal activity".
According to the negative feedback principle,
increased neuronal activity causes accumulation of vasoactive catabolites, such
as H+, K+, and adenosine. These substances decrease vascular resistance and
increase the blood flow, until the normal hemostasis is achieved. Studies have
found that stimulation of nerves, such as that with flicker stimuli, leads to
activity-dependent regulation of OBF in the retina and ONH. In glaucomatous
eyes, astrocytic dysfunction in the ONH can disrupt this coupling, leading to
retinal ganglion cell stress and degeneration independently or in association
with changes in IOP. Malfunctioning of the astrocytes and disturbed
neurovascular coupling triggers structural remodeling in the ONH, which appears
as optic disc cupping.
Neurogenic
Control of Vessels
The eye has a rich supply of autonomic nerves within the
uvea, the posterior ciliary arteries, and the extraocular portion of the
central retinal artery. Vessels in the retina and the prelaminar portion of the
optic nerve have no neural innervation. Consequently, stimulation of the sympathetic
nerve system might influence retinal and optic nerve head perfusion indirectly,
at most. Nevertheless, α- and β-adrenergic receptors have been demonstrated in
the retinal vessels.
The autonomic
nervous system supplies a network of vasomotor nerve fibers. The nerve fibers
form a plexus in the adventitia of the resistance vessel walls and send
extensions to form varicosities on the outer surface of the media.
The nerve
fibers consist of three kinds of fibers: (a) adrenergic; (b) cholinergic; and
(c) non-adrenergic/non-cholinergic (nitric oxide).
Neurotransmitters
are released from the varicosities towards the smooth muscle cells. Norepinephrine
produces vasoconstriction by stimulating alpha-receptors, and acetylcholine
evokes vasodilatation by stimulating M3-receptors. In addition to these
classical neurotransmitters, several substances are released in the nerve
terminals.
Stimulation of the sympathetic superior cervical ganglion
elicits constriction of the uveal blood vessels and increases the uveal
vascular resistance. Surprisingly, electrical stimulation of parasympathetic
fibers of the ciliary ganglion induces intense miosis, without notably changing
the uveal vascular resistance. Intracranial stimulation of the oculomotor nerve
produces vasoconstriction in the anterior uvea and vasodilation in the choroid.
Uveal vasodilation is also seen on stimulation of the facial
nerve and ophthalmic and maxillary divisions of the trigeminal nerve.
Vasoactive intestinal polypeptide (VIP)-immunoreactive
nerves have been demonstrated in the choroid, indicating that VIP may be
involved in the vasodilation produced by nerve stimulation.
The dense vasodilative innervation of the choroid, might
be important to increase choroidal blood flow under certain conditions such as
high light intensity.
Microvascular unit techniques combining bi-directional laser Doppler velocimetry and retinal vessel analyzer (RVA) confirmed human retinal blood flow response to flicker light measuring an increase of retinal blood flow in the magnitude of 53--59%.
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